Amino acid-based biodegradable PEAs have been studied for many years due to their biocompatibility, biodegradability and mechanical properties. The presence of amide and ester bonds in PEA furnishes the PEA with a combination of properties typically exhibited by either polyesters or polyamides. Biodegradable PEA is typically synthesized by a solution polycondensation reaction of a-amino acids, aliphatic dicarboxylic acids (or dichloride of dicarboxylic acids) and diols (see Guo et al., Journal of Polymer Science, Part A: Polymer Chemistry 2007, 45(9): 1595-1606).
PEA homopolymers generally do not have any functional groups located either along the PEA backbone chain or as pendant groups. The first reported synthesis of functional PEAs was based on a copolymer approach. A free functional group in the form of a carboxylic acid group was introduced in the lysine segment of the PEA copolymer. (See, Jokhadze et al., Journal of Biomaterials Science—Polymer Edition 2007; 18(4):411-438.) In another approach, carbon-to-carbon double bonds have been positioned along the backbone of PEA to provide a reactive site for the introduction of a functional group into PEA via unsaturated diacids and/or diols.
Delivery of desired biomolecules to cells can be accomplished by various delivery means that generally fall into 4 broad categories: water soluble cationic polymers, lipids, dendrimers and nanoparticles. Among them, the water soluble synthetic and natural polycations have attracted the most attention. A large number of cationic polymers have been tested for gene delivery. Among them, poly-L-lysine (PLL) and polyethylenimine (PEI) have been intensively studied because of their strong interaction with the plasmid DNA which results in formation of a compact polymer/DNA complex. Other synthetic and natural polycations developed as non-viral vectors includes polyamidoamine dendrimers and chitosan, imidazole-containing polymers with proton-sponge effect, membrane-disruptive peptides and polymers like polyethylacrylic acid (PEAA), poly [alpha-(4-aminobutyl)-L-glycolic acid] (PAGA), and poly (amino acid) based materials. However, most of them could not achieve both high transfection efficiency and low toxicity.